Modified Dental Prosthesis

ABSTRACT

Phosphate-containing co-polymers useful for making denture bases, denture liners and tissue conditioners with phosphate anion-charged surfaces are disclosed. The phosphate anions enable the denture bases, denture liners and tissue conditioners to adsorb cationic antimicrobial molecules. Dentures, denture bases materials, denture liners and tissue conditioners made of the above co-polymers are also disclosed. Further disclosed are methods for synthesizing the co-polymer(s) and for making the denture bases, denture liners and tissue conditioners.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. application Ser.No. 10/799,477 filed on Mar. 12, 2004, which claims the benefit of theU.S. provisional application Ser. No. 60/455,024, filed on Mar. 14,2003.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not applicable.

BACKGROUND OF THE INVENTION

Denture-induced stomatitis is a common clinical condition characterizedby oral mucosal lesions, and is prevalent among denture users,particularly elderly or institutionalized patients. Adherence of Candidaalbicans to denture surfaces is the primary cause of denture-inducedstomatitis. Other microbial species reported to contribute to thecondition include Streptococcus oralis, Streptococcus sanguis,Porphyromonas gingivalis and Prevotella intermedia. Treatment ofdenture-induced stomatitis is problematic due to incomplete disinfectionof the surface and rapid microbial recolonization of the dentalprosthesis.

Typically, “pellicles,” which contain high molecular weight salivaryglycoproteins and immunoglobulins, including mucins, amylase andsecretory IgA together with natural cationic antimicrobial peptides,form a thin film on surfaces of the oral cavity. On non-prostheticsurfaces, antimicrobial peptides such as histatins, defensins, andbactenecins, derived from saliva, mucosal epithelial cells andneutrophils, are a key protective component of the mucosal and enamelpellicles. Histatins and bactenecins, in particular, have been shown toexhibit antifungal and antibacterial activity against Candida albicansand other oral pathogens. These cationic peptides are adsorbed onto thetooth and oral mucosal surfaces by electrostatic forces.

In contrast, protective antimicrobial peptides are not present in thepellicle which forms on the denture surfaces. Dentures areconventionally made of polymethyl methacrylate (PMMA), which has polarester groups but no ionically charged groups. The absence of ioniccharge on PMMA facilitates the adhesion of Candida albicans and othermicrobial species onto denture surfaces by preventing the selectiveadsorption of antimicrobial peptides in saliva to prosthetic surfaces.

Introducing carboxylate groups into PMMA-based denture material toprovide carboxylate ions on the surface has been shown to enhanceadsorption of histatins and to decrease adherence of Candida albicans todenture surfaces (Edgerton, M., Raj, P. A., and Levine, M. J., J.Biomed. Mat. Res. 29:1277-1286, 1995; and Raj, P. A., and Venkataraman,G., Dent. Res. 80: 51, 2001). However, it is not known whether othergroups such as phosphate groups can be successfully introduced intodenture bases to provide negatively charged surfaces, and further,whether anionic phosphate surfaces have the ability to substantiallyenhance antimicrobial molecule adsorption as well as microbial adherenceinhibition, especially under physiological conditions.

BRIEF SUMMARY OF THE INVENTION

In one aspect, the present invention relates to a phosphate-containingco-polymer useful for making a denture base, denture liner or tissueconditioner with a negatively charged surface for adsorbing cationicantimicrobial molecules such as salivary antimicrobial peptides. Theco-polymer contains a repeating unit derived from an alkyl or arylmethacrylate monomer and a repeating unit derived from aphosphate-containing monomer having the formula

wherein X is either —O—PH₂O₃ or —R—O—PH₂O₃. The R group in —R—O—PH₂O₃ iseither —COO—CH₂—CH₂ or a straight or branched alkyl chain of 10 carbonatoms or less. The two methylene groups in —COO—CH₂—CH₂ and the alkylcarbon chain can be substituted with an aryl group, a cycloalkyl groupor both.

In another aspect, the present invention relates to a denture base,denture liner or tissue conditioning material made of the co-polymerdescribed above. A denture having a denture base made of the co-polymerdescribed above is also within the scope of the present invention.

In still another aspect, the present invention relates to a method forsynthesizing the co-polymer described above or for making a denturebase, denture liner or tissue conditioner containing the co-polymer.

In yet another aspect, the present invention relates to a kit thatcontains an antimicrobial solution for use with the denture of thepresent invention and an instruction sheet on how to treat the denturewith the solution. Optionally, a denture of the present invention isalso included in the kit.

It is an object of the present invention to provide a denture base,denture liner or tissue conditioner with a negatively charged surfacefor adhesion of cationic anti-microbial molecules.

It is a feature of the present invention that the charge on the surfaceof the denture base, denture liner or tissue conditioner is provided bya phosphate group.

It is an advantage of the present invention that the phosphate anions onthe surface of the denture base, denture liner or tissue conditioner arethe naturally occurring negatively charged molecules on the tooth enamelsurface and normal oral tissues.

Other objects, advantages and features of the present invention willbecome apparent from the following specification.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 is a graph showing the adsorption of bactenecin 5 on PMMApolymers. Adsorption is determined as a function of amount adsorbedversus nanograms added to PMMA beads.

FIG. 2 is a graph showing the adsorption of histatin 5 on PMMA polymers.Adsorption is determined as a function of amount adsorbed versusnanograms added to PMMA beads. PMMA: MMA:MAP=100:0; PMMA1: MMA:MAP=95:5;PMMA2: MMA:MAP=90:10; PMMA3: MMA:MAP=85:15; PMMA4: MMA:MAP=80:20; PMMA5:MMA:MAP=75:25.

FIG. 3 is a graph showing adhesion of Candida albicans to histatin5-adsorbed PMMA polymer surfaces. Adhesion is determined as a functionof number of cells added versus number of cells bound per milligram ofpolymer.

FIG. 4 is a graph showing Candidacidal activity of bactenecin 5-adsorbedpolymers. Candidacidal activity is determined as a ftunction of percentcalcein released from calcein-loaded cell per minute.

DETAILED DESCRIPTION OF THE INVENTION

It is disclosed here that a polyalkyl methacrylate- or polyarylmethacrylate-based denture base, denture liner or tissue conditioner canbe improved by incorporating into the polymer a phosphate-containingmonomer defined herein below. The phosphate group provides the denturebase, denture liner or tissue conditioner with a negatively chargedsurface, which can readily adsorb salivary antimicrobial peptides andthus help to reduce the microbial infection rate in denture users.Polyalkyl methacrylate- and polyaryl methacrylate-based denture bases,denture liners and tissue conditioners are collectively referred to asPMMA-based denture bases, denture liners and tissue conditioners for thepurposes of the present invention. Examples of PMMA-based denture bases,denture liners and tissue conditioners as well as polymers and methodsfor making them can be found in Phillip's Science of Dental Materials,Anusavice, K. D. ed., W.B. Saunders Company, Philadelphia, Pa., 1996,incorporated herein by reference as if set forth in its entirety.Additional PMMA-based denture bases and denture liners as well aspolymers and methods for making them are also known in the art. UsingPMMA-based denture base and phosphate-containing monomers methallaylphosphate (MAP) and ethylene glycol methacrylate phosphate (EGMP) asexamples, the inventors demonstrated in the examples below thatincorporating a phosphate-containing monomer of the present inventioninto the denture base polymer substantially improved the polymer'sability to adsorb antimicrobial peptides. As a result, microbialcolonization on the polymer was inhibited. The examples below furtherdemonstrated that incorporating a phosphate-containing monomer of thepresent invention into a PMMA polymer would not substantially affect thephysical and mechanical properties of the polymer such as flexuralstrength.

The phosphate-containing monomer of the present invention is defined bythe following formula:

wherein X is either —O—PH₂O₃ or —R—O—PH₂O₃. The R group in —R—O—PH₂O₃ iseither —COO—CH₂—CH₂ or a straight or branched alkyl chain of 10 carbonatoms or less. The two methylene groups in —COO—CH₂—CH₂ and the alkylcarbon chain can be substituted with an aryl group, a cycloalkyl groupor both.

In a preferred embodiment, the R group is CH₂ and the monomer is MAP. Inanother preferred embodiment, the R group is CH₂CH₂COO and the monomeris EGMP.

The monomers defined by formula (I) are either commercially available(e.g, EGMP can be obtained from Aldrich, Milwaukee, Wis.) or can bereadily synthesized by a skilled artisan. For example, MAP can besynthesized from methyl methacrylate (MMA). MMA is first reduced tomethallyl alcohol and methallyl alcohol is then phosphorylated togenerate MAP. The reducing step can be performed with NaBH₄/EtOH orother reducing agents capable of reducing the ester moiety of MMA. Thephosphorylation step can be performed with N,N-diethylphosphoramidite inthe presence of 1-H-tetrazole followed by oxidation withm-chloroperbenzoic acid.

The co-polymer of the present invention contains a first repeating unitderived from an alkyl or aryl methacrylate monomer and a secondrepeating unit derived from the phosphate-containing monomer defined byformula (I). Preferably, the first repeating unit is derived from analkyl or aryl methacrylate monomer that has 10 carbon atoms or less.More preferably, the first repeating unit is derived from MMA. Adenture, denture base, denture liner or tissue conditioner made of theco-polymer is also within the scope of the present invention.

The co-polymer of the present invention can be synthesized by providingthe two monomers and exposing the monomers to polymerization conditionsunder which the monomers polymerize to form the co-polymer. Suchpolymerization conditions are either familiar to or can be readilydetermined by a skilled artisan depending on the particular monomersused.

Alternatively, the co-polymer can be synthesized by providing apre-polymerized polymer and the two monomers, and exposing thepre-polymerized polymer and the monomers to polymerization conditionsunder which they polymerize to form the co-polymer. Again, suitablepolymerization conditions are either familiar to or can be readilydetermined by a skilled artisan depending on the particularpre-polymerized polymer and the monomers used. The pre-polymerizedpolymer can be a PMMA polymer, or a co-polymer containing a repeatingunit derived from an alkyl or aryl methacrylate monomer and a repeatingunit derived from a formula (I) monomer.

The above alternative method is the preferred method for making denturebases. Typically, in making denture bases, the pre-polymerized polymeris provided as polymer beads (powder) supplemented with a polymerizationinitiator and the monomers are provided as a liquid supplemented with apolymerization inhibitor for preventing undesirable polymerization. Thepolymer beads and the monomer liquid are mixed and heat-cured to producea denture base. Preferably, the polymer beads and the monomer liquid aremixed at a ratio of about 3 to 1 (volume/volume) to minimizepolymerization shrinkage. More details and examples of the beadsuspension polymerization technique can be found in Phillip's Science ofDental Materials, Anusavice, K. D. ed., W.B. Saunders Company,Philadelphia, Pa., 1996.

In order to substantially maintain the physical and mechanicalproperties of a denture base, the amount of the phosphate-containingmonomers incorporated into the PMMA polymer should be controlled.Preferably, the molar ratio of a repeating unit derived from thephosphate-containing monomer to a repeating unit derived from the alkylor aryl methacrylate monomer in the final co-polymer should be equal toor less than 40:60, 35:65, 30:70, 25:75, 20:80, 15:85, 10:90, 5:95, 3:97or 1:99. When EGOMP is used to form a co-polymer with MMA for making adenture base, the molar ratio of EGMP to MMA is preferably to be 10:90or less, 5:95 or less, or 3:97 or less. If necessary, the physical andmechanical properties of a new phosphate-containing co-polymer can bereadily tested by a skilled artisan and compared to those of aconventional denture base, such as a PMMA denture base, following theADA/ISO Specifications ((ISO 1567:1999 (E)). Examples of physical andmechanical properties that can be tested and compared include watersorption, solubility, porosity, residue monomer, hardness, flexuralstrength, transverse strength, transverse deflection, and moduluselasticity. Denture liners are made more flexible than denture basestypically through the incorporation of large plasticizer molecules.Another type of dental prosthesis for lining dentures is tissueconditioners, which are softener and more flexible than denture liners.Tissue conditioners are used to line dentures to make them morecomfortable and are particularly useful for relieving trauma caused bythe denture rubbing on the inflamed tissues (e.g., in stomatitis). It isexpected that a higher percentage of phosphate-containing monomers canbe incorporated into denture liner and tissue conditioner co-polymerswithout substantially affecting a denture liner's physical andmechanical properties.

Most denture users have normal salivary functions and thus can readilybenefit from the improved denture bases, denture liners and tissueconditioners disclosed herein. Some denture users, however, haveimpaired salivary functions characterized by the reduced level ofsalivary antimicrobial peptides. For these users, dentures, dentureliners and tissue conditioners can be soaked in an antimicrobialsolution before use. The antimicrobial solution is a solution thatcontains one or more antimicrobial agents that can be adsorbed onto anegatively charged surface. Examples of such antimicrobial agentsinclude but are not limited to cationic antimicrobial proteins andactive peptide fragments thereof. Preferred antimicrobial agents aresalivary anti-microbial peptides such as histatins, defensins andbactenecins. The antimicrobial solution and one or more of a denture,denture liner and tissue conditioning materials can be convenientlyprovided as a kit to denture users and/or dental professionals. When theusers run out of the antimicrobial solution, they can be resupplied witha kit containing an antimicrobial solution and instructions on how totreat a denture with the solution. Recently, the inventors have designedintra-oral drug delivery molecules that selectively adsorb onto chargedsurfaces and gradually release antimicrobial peptides over time (U.S.patent application Ser. No. 10/704,171, filed on Nov. 7, 2003,incorporated herein by reference as if set forth in its entirety). Thisintra-oral drug delivery system and a denture disclosed herein can alsobe provided as a kit to dental professionals.

It is appreciated that in addition to making denture bases, dentureliners and tissue conditioners, the monomers and co-polymers disclosedherein can also be used to repair damaged denture bases, and to relineor rebase existing dentures.

The following examples are given to further illustrate the presentinvention. The present invention is not limited to the specific detailsset forth in the examples.

EXAMPLE 1 Preparation of Denture Base Polymers with Various PhosphateContent

Synthesis of polymers of MMA and MAP: Mixtures of MMA and MAP [MMA:MAP;100:0; 95:5; 90:10; 85:15; 80:20; 75:25] in molar ratio were used asmonomers. Bead (suspension) polymerization techniques were employed. Ina 50 ml flask, 35 g of monomer mixture was stirred with 1.2 g of benzoylperoxide (well ground). Then 0.75 ml of dimethyl paratoluidine was addedand stirred briefly. The mixture was poured into 250 ml flask containing1% poly (vinyl alcohol) and stirred well to prevent separation of twolayers and the temperature was recorded. The reaction was allowed toproceed for 15 min after the rise in temperature ceased. The polymerbeads were filtered, washed with distilled water and dried.

Characterization of polymer beads: The synthesized polymers wereexamined for the incorporation of phosphate by using FTIR and NMRstudies. The polymers were checked for ³¹P NMR resonance and examined byFTIR for changes in the region 1000-1200 cm⁻¹ (P═O and P—O IR bands).The polymers were dissolved in a mixture of chloroform and dimethylsulfoxide for spectroscopic studies.

Synthesis of polymers of MMA and EGMP: Polymers with varying amounts ofphosphate were synthesized using mixtures of MMA and EGMP as monomersdescribed in the following molar ratios [MMA:EGMP; 100:0; 95:5; 90:10;85:15; 80:20; 75:25]. Standard bead (suspension) polymerizationtechnique described above in connection with the synthesis of polymersof MMA and MAP was employed, since the rate of polymerization can bewell controlled through the cooling action of water. Polymer beads withan average molecular weight of the order of approximately 1 million kDawere obtained by this method.

EXAMPLE 2 Adsorption of Antimicrobial Peptides

Histatin 5 and bactenecin 5 adsorption experiments were conducted asdescribed in Edgerton, M., Raj, P. A., and Levine, M. J. J. Biomed.Biomat. Res. 29: 1277-1286, 1995, and Raj, P. A., Johnsson, M., Levine,M. J., and Nancollas, G. H. J. Biol. Chem. 267: 5968-5976, 1992, both ofwhich are herein incorporated by reference in their entirety. Thepolymer beads produced in accordance with Example 1 were equilibrated atroom temperature for 2 hours with peptides (histatin 5 and bactenecin 5)of varying concentrations. The equilibration buffer employed was asaliva buffer that had the same ionic strength as that of human salivaand the same pH of 7.2 as that of the human oral cavity. The polymerbeads were separated by centrifugation and the amount of peptides leftin the supernatant was measured. The amount of the peptides adsorbed wasthen determined by subtracting the amount of peptides in the supernatantfrom the total amount peptides provided in the equilibration solution.When a relatively small amount of peptides was used in the experiments,¹²⁵[I] peptides were used so that the amount of peptides could bemeasured by radioactivity. When a relatively large amount of peptideswas used in the experiments, unlabeled peptides were used and the amountof peptides in the supernatant was determined by amino acid analysis.

As shown in FIG. 1 and FIG. 2, increased adsorption of antimicrobialagents was correlated with increases in the negative charge on thepolymer as the molar ratio of MAP in the PMMA co-polymer was increased.The result in FIG. 1 demonstrates increased adsorption of histatin 5.FIG. 2 shows that similar results were observed with bactenecin 5.

EXAMPLE 3 Adherence of Candida Albicans

Saliva-coated polymer beads were prepared as described in Edgerton, M.,Raj, P. A., and Levine, M. J. J. Biomed. Biomat. Res. 29: 1277-1286,1995. The saliva-coated polymers were allowed to adsorb histatin 5 asdescribed in the Example 2. These histatin 5 adsorbed polymers were thenincubated with ³⁵[S]-labeled Candida albicans blastospore (strain DS1isolated from the palate of a denture patient) at 10⁸ cells/ml in thesaliva buffer described in Example 2. The incubation was conducted at25° C. for 2 hours. Polymer beads were then recovered by centrifugationand the radioactivity of the polymer beads was determined. Adherence wascalculated as the number of cells bound to the beads minus thebackground.

The results shown in FIG. 3 demonstrated that the adherence of Candidaalbicans to PMMA surfaces decreased with increases in negative charge.

EXAMPLE 4 Candidacidal Activity

Fluorescence spectroscopy was used to determine the Candidacidalactivity of the peptide-adsorbed PMMA surface. Candida albicans (strainDS1) was incubated with calcein AM, a widely used green fluorescent cellmarker. Calcein AM is membrane-permeant, and thus can be introduced intocells via incubation. Once inside cells, calcein AM is hydrolyzed byendogenous esterase into the highly negatively charged green fluorescentcalcein, which is retained in the cytoplasm. Polymer beads produced bythe method of Example 1 were coated with 250 μM bactenecin 5 andincubated with the calcein AM-labeled DS 1. The release of calcein wasmonitored by fluorescence measurements of the suspension as an indicatorof Candidacidal activity (Edgerton, M., Raj, P. A., and Levine, M. J. J.Biomed. Biomat. Res. 29: 1277-1286, 1995).

The results shown in FIG. 4 demonstrated that Candidacidal activity ofthe polymer increased with the increase in negative charge.

EXAMPLE 5 Flexural Strength of Denture Base Materials Made of MMA/EGMPPolymer

Flexural strength of denture base materials made of MMA/EGMP polymerswere tested according to the ISO standards. The MMA/EGMP polymers weresynthesized by using PMMA polymer beads and a mixture of MMA and EGMPmonomers. The MMA and EGMP monomers were provided in the monomer mixturein a ratio such that the weight ratio of MMA-derived repeating unit toEGMP-derived repeating unit in the final MMA/EGMP polymer was about80:20 (referred to as E20 polymer) or about 90:10 (referred to as E10polymer). Specimen plates were prepared and machined to the dimensionalspecifications (50 mm length×10 mm width×3.3 mm height) within 0.02 mm.Before testing the specimens were stored in water at 37° C. for 50 hoursand were tested under water by loading with a cross head speed 5±1mm/min.

Table 1 shows the averages and standard deviations of flexural strength(MPa units) for denture base materials made of E20 and E10 polymers incomparison to a commercially available standard (Lucitone-99).Incorporating up to 10% (weight) and 20% (weight) EGMP into PMMA reducedthe flexural strength by only 7% and 13%, respectively. TABLE 1 SpecimenE20-MPa E10-MPa C-MPa 1 64.07 64.20 77.95 2 65.60 66.52 75.73 3 59.1865.81 65.22 4 64.52 71.69 74.84 5 64.71 69.49 74.46 6 56.57 63.89 64.77Mean 62.44 66.94 72.16 SD 3.67 3.08 5.68 CV 5.87 4.60 7.88 SD = StandardDeviation CV = Coefficient of Variation t-Test Results: Groups p ValueE20:E10 0.0094 E20:C 0.0001 E10:C 0.0319

The present invention is not intended to be limited to the foregoingexamples, but to encompass all such modifications and variations as comewithin the scope of the appended claims.

1. A denture base comprising: (i) a co-polymer comprising a firstrepeating unit derived from an alkyl or aryl methacrylate monomer and asecond repeating unit derived from a phosphate-containing monomer havingthe formula

wherein X is selected from —O—PH₂O₃ and —R—O—PH₂O₃, wherein the R groupin —R—O—PH₂O₃ is selected from —COO—CH₂—CH₂ and a straight or branchedalkyl chain of 10 carbon atoms or less, wherein the two methylene groupsin —COO—CH₂—CH₂ and the alkyl carbon chain can be substituted with anaryl group, a cycloalkyl group or both, wherein the molar ratio of saidfirst repeating unit to said second repeating unit in the co-polymer is60 to 40 or higher; and (ii) an antimicrobial agent absorbed to thesurface of the denture base in an amount effective to reduce the numberof bacteria residing on the denture surface.
 2. The denture base ofclaim 1, wherein the first repeating unit is derived from an alkyl oraryl methacrylate monomer that has 10 carbons or less.
 3. The denturebase of claim 1, wherein the first repeating unit is derived from methylmethacrylate.
 4. The denture base of claim 1, wherein the secondrepeating unit is derived from methallyl phosphate.
 5. The denture baseof claim 1, wherein the second repeating unit is derived from ethyleneglycol methacrylate phosphate.
 6. The denture base of claim 1, whereinthe molar ratio of the first repeating unit to the second repeating unitis at least 70 to
 30. 7. The denture base of claim 1, wherein the molarratio of the first repeating unit to the second repeating unit is atleast 75 to
 25. 8. The denture base of claim 1, wherein the molar ratioof the first repeating unit to the second repeating unit is at least 80to
 20. 9. The denture base of claim 1, wherein the antimicrobial agentis a cationic antimicrobial polypeptide.
 10. The denture base of claim9, wherein the antimicrobial agent is selected from a histatin, adefensin, and a bactenecin.
 11. A kit comprising: (i) a denture basethat comprises a co-polymer comprising a first repeating unit derivedfrom an alkyl or aryl methacrylate monomer and a second repeating unitderived from a phosphate-containing monomer having the formula

wherein X is selected from —O—PH₂O₃ and —R—O—PH₂O₃, wherein the R groupin —R—O—PH₂O₃ is selected from —COO—CH₂—CH₂ and a straight or branchedalkyl chain of 10 carbon atoms or less, wherein the two methylene groupsin —COO—CH₂—CH₂ and the alkyl carbon chain can be substituted with anaryl group, a cycloalkyl group or both, wherein the molar ratio of saidfirst repeating unit to said second repeating unit in the co-polymer is60 to 40 or higher; (ii) a solution that contains an antimicrobial agentfor treating the denture base; and (iii) an instruction manualdescribing how to use the solution to treat the denture base.
 12. Thekit of claim 11, wherein the first repeating unit is derived from analkyl or aryl methacrylate monomer that has 10 carbons or less.
 13. Thekit of claim 11, wherein the first repeating unit is derived from methylmethacrylate.
 14. The kit of claim 11, wherein the second repeating unitis derived from methallyl phosphate.
 15. The kit of claim 11, whereinthe second repeating unit is derived from ethylene glycol methacrylatephosphate.
 16. The kit of claim 11, wherein the molar ratio of the firstrepeating unit to the second repeating unit is at least 70 to
 30. 17.The kit of claim 11, wherein the molar ratio of the first repeating unitto the second repeating unit is at least 75 to
 25. 18. The kit of claim11, wherein the molar ratio of the first repeating unit to the secondrepeating unit is at least 80 to
 20. 19. The kit of claim 11, whereinthe antimicrobial agent is a cationic antimicrobial polypeptide.
 20. Thekit of claim 19, wherein the antimicrobial agent is selected from ahistatin, a defensin, and a bactenecin.
 21. A method for making adenture base, the method comprising the steps of: providing apre-polymerized polymer resin suitable for making the denture base, anda liquid comprising an alkyl or aryl methacrylate monomer and aphosphate-containing monomer having the formula

wherein X is selected from the group consisting of —O—PH₂O₃ and—R—O—PH₂O₃, wherein the R group in —R—O—PH₂O₃ is selected from the groupconsisting of —COO—CH₂—CH₂ and a straight or branched alkyl chain of 10carbon atoms or less, wherein the two methylene groups in —COO—CH₂—CH₂and the alkyl carbon chain can be substituted with an aryl group, acycloalkyl group or both; and mixing the pre-polymerized polymer resinwith the liquid under conditions that allow the pre-polymerized polymerand the monomers to polymerize to form a denture base comprising aco-polymer that comprises a first repeating unit derived from the alkylor aryl methacrylate monomer and a second repeating unit derived fromthe phosphate-containing monomer wherein the molar ratio of said firstrepeating unit to said second repeating unit in the co-polymer is 60 to40 or higher.
 22. The method of claim 21, wherein the first repeatingunit is derived from an alkyl or aryl methacrylate monomer that has 10carbons or less.
 23. The method of claim 21, wherein the first repeatingunit is derived from methyl methacrylate.
 24. The method of claim 21,wherein the second repeating unit is derived from methallyl phosphate.25. The method of claim 21, wherein the second repeating unit is derivedfrom ethylene glycol methacrylate phosphate.
 26. The method of claim 21,wherein the molar ratio of the first repeating unit to the secondrepeating unit is at least 70 to
 30. 27. The method of claim 21, whereinthe molar ratio of the first repeating unit to the second repeating unitis at least 75 to
 25. 28. The method of claim 21, wherein the molarratio of the first repeating unit to the second repeating unit is atleast 80 to
 20. 29. The method of claim 21, wherein the pre-polymerizedpolymer is a polymethyl methacrylate (PMMA) polymer.
 30. The method ofclaim 21, wherein the pre-polymerized polymer is a co-polymer containinga first repeating unit derived from the alkyl or aryl methacrylatemonomer and a second repeating unit derived from thephosphate-containing monomer.